tbuckley/cabot-search huggingface dataset:
Rotavirus-Associated Hospitalization in Children With Subsequent Autoimmune Disease
Authors: Eun Kyo Ha, Ju Hee Kim, Hye Ryeong Cha, Gi Chun Lee, Jeewon Shin, Youn Ho Shin, Hey-Sung Baek, Seung Won Lee, Man Yong Han
Journal: JAMA Network Open (2023)

Importance Rotavirus infection is a common cause of gastroenteritis in children that can trigger autoimmune processes, but the nature of this interaction remains poorly understood. Objective To estimate the association of rotavirus infection with the risk of subsequent autoimmune disease. Design, Setting, and Participants This population-matched cohort study used data from children and adolescents (aged younger than 18 years) in South Korea (national registers from January 1, 2002, to December 31, 2017). The cohort consisted of 86 157 patients in the exposure group who had experienced rotavirus-associated hospitalization and the same number of matched patients in the unexposed group. Data analyses were from May 1, 2020, through October 20, 2022. Exposures Hospitalization for rotavirus infection. Main Outcomes and Measures The main outcome was childhood autoimmune diseases during the study defined by diagnoses according to the National Health Insurance Database. Hazard ratios (HRs) with 95% CIs for autoimmune diseases were estimated using a Cox model, with multiple confounding factors controlled. Results This cohort study consisted of 1 914 461 individuals born in South Korea from 2002 to 2005 who were potentially eligible. After exclusions, there were 86 517 individuals in the exposed group and 86 517 in the unexposed group after 1:1 incidence density sampling. The study included 49 072 (57.0%) male patients. The median (IQR) age at diagnosis of rotavirus-associated hospitalization was 1.5 (0.9-2.7) years, and the HR for autoimmune disease in the exposed group was 1.24 (95% CI, 1.19-1.28) for a mean (SD) follow-up time of 12.1 (3.2) years. The use of more stringent definitions for exposure and outcomes in a multivariable stratified analysis also indicated that rotavirus-associated hospitalization was associated with an increased risk of subsequent autoimmune disease (HR, 1.22 [95% CI, 1.16-1.28]). Sensitivity analysis showed that individuals with rotavirus-associated hospitalization was related to multiple autoimmune syndromes (2 or more: HR, 1. 51 [95% CI, 1. 31-1. 73]; 3 or more: HR, 1. 79 [95% CI, 1.18-2.72]) and that the number of rotavirus-associated hospitalization were associated with higher risks for autoimmune disease in a dose-dependent manner (single hospitalization event: HR, 1.20 [95% CI, 1.16-1.24]; multiple events HR, 1.60 [95% CI, 1.49-1.72]). Conclusions and Relevance Our results indicate that rotavirus-associated hospitalization is significantly associated with subsequent autoimmune disease during childhood. Clinicians should be aware of the heightened susceptibility to autoimmune disease in individuals with prior rotavirus-associated hospitalization.
Troponins and Pregnancy
Authors: Eva Furenäs, Mikael Dellborg
Journal: JAMA Cardiology (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Cardiology HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Cardiology journal
Association of Longer Leukocyte Telomere Length With Cardiac Size, Function, and Heart Failure
Authors: Nay Aung, Qingning Wang, Stefan van Duijvenboden, Richard Burns, Svetlana Stoma, Zahra Raisi-Estabragh, Selda Ahmet, Elias Allara, Angela Wood, Emanuele Di Angelantonio, John Danesh, Patricia B. Munroe, Alistair Young, Nicholas C. Harvey, Veryan Codd, Christopher P. Nelson, Steffen E. Petersen, Nilesh J. Samani
Journal: JAMA Cardiology (2023)

Importance Longer leukocyte telomere length (LTL) is associated with a lower risk of adverse cardiovascular outcomes. The extent to which variation in LTL is associated with intermediary cardiovascular phenotypes is unclear. Objective To evaluate the associations between LTL and a diverse set of cardiovascular imaging phenotypes Design, Setting, and Participants This is a population-based cross-sectional study of UK Biobank participants recruited from 2006 to 2010. LTL was measured using a quantitative polymerase chain reaction method. Cardiovascular measurements were derived from cardiovascular magnetic resonance using machine learning. The median (IQR) duration of follow-up was 12.0 (11.3-12.7) years. The associations of LTL with imaging measurements and incident heart failure (HF) were evaluated by multivariable regression models. Genetic associations between LTL and significantly associated traits were investigated by mendelian randomization. Data were analyzed from January to May 2023. Exposure LTL. Main Outcomes and Measures Cardiovascular imaging traits and HF. Results Of 40 459 included participants, 19 529 (48.3%) were men, and the mean (SD) age was 55.1 (7.6) years. Longer LTL was independently associated with a pattern of positive cardiac remodeling (higher left ventricular mass, larger global ventricular size and volume, and higher ventricular and atrial stroke volumes) and a lower risk of incident HF (LTL fourth quartile vs first quartile: hazard ratio, 0.86; 95% CI, 0.81-0.91; P = 1.8 × 10 −6 ). Mendelian randomization analysis suggested a potential causal association between LTL and left ventricular mass, global ventricular volume, and left ventricular stroke volume. Conclusions and Relevance In this cross-sectional study, longer LTL was associated with a larger heart with better cardiac function in middle age, which could potentially explain the observed lower risk of incident HF.
Impact of cytogenetic abnormalities on the risk of disease progression in solitary bone plasmacytomas
Authors: Udit Yadav, Shaji K. Kumar, Linda B. Baughn, Angela Dispenzieri, Patricia Greipp, Rhett Ketterling, Dragan Jevremovic, Francis K. Buadi, David Dingli, Martha Q. Lacy, Rafael Fonseca, P. Leif Bergsagel, Sikander Ailawadhi, Vivek Roy, Ricardo Parrondo, Taimur Sher, Suzanne R. Hayman, Prashant Kapoor, Nelson Leung, Joselle Cook, Moritz Binder, Eli Muchtar, Rahma Warsame, Taxiarchis V. Kourelis, Ronald S. Go, Yi Lin, Abhishek Seth, Scott C. Lester, William G. Breen, Robert A. Kyle, Morie A. Gertz, S. Vincent Rajkumar, Wilson I. Gonsalves
Journal: Blood (2023)
Dual pH and microbial-sensitive galactosylated polymeric nanocargoes for multi-level targeting to combat ulcerative colitis
Authors: Mahira Zeeshan, Qurat Ul Ain, Benno Weigmann, Darren Story, Bryan R. Smith, Hussain Ali
Journal: Asian Journal of Pharmaceutical Sciences (2023)

Ulcerative colitis (UC) is a type of inflammatory bowel disease characterized by inflammation, ulcers and irritation of the mucosal lining. Oral drug delivery in UC encounters challenges because of multifaceted barriers. Dexamethasone-loaded galactosylated-PLGA/Eudragit S100/pullulan nanocargoes (Dexa-GP/ES/Pu NCs) have been developed with a dual stimuli-sensitive coating responsive to both colonic pH and microbiota, and an underneath galactosylated-PLGA core (GP). The galactose ligand of the GP preferentially binds to the macrophage galactose type-lectin-C (MGL-2) surface receptor. Therefore, both stimuli and ligand-mediated targeting facilitate nanocargoes to deliver Dexa specifically to the colon with enhanced macrophage uptake. Modified emulsion method coupled with a solvent evaporation coating technique was employed to prepare Dexa-GP/ES/Pu NCs. The nanocargoes were tested using in vitro, ex vivo techniques and dextran sodium sulfate (DSS) induced UC model. Prepared nanocargoes had desired physicochemical properties, drug release, cell uptake and cellular viability. Investigations using a DSS-colitis model showed high localization and mitigation of colitis with downregulation of NF-ĸB and COX-2, and restoration of clinical, histopathological, biochemical indices, antioxidant balance, microbial alterations, FTIR spectra, and epithelial junctions' integrity. Thus, Dexa-GP/ES/Pu NCs found to be biocompatible nanocargoes capable of delivering drugs to the inflamed colon with unique targeting properties for prolonged duration.
Preclinical Efficacy of LP-184, a Tumor Site Activated Synthetic Lethal Therapeutic, in Glioblastoma
Authors: Bachchu Lal, Aditya Kulkarni, Joseph McDermott, Rana Rais, Jesse Alt, Ying Wu, Hernando Lopez-Bertoni, Sophie Sall, Umesh Kathad, Jianli Zhou, Barbara S. Slusher, Kishor Bhatia, John Laterra
Journal: Clinical Cancer Research (2023)

Glioblastoma (GBM) is the most common brain malignancy with median survival <2 years. Standard-of-care temozolomide has marginal efficacy in approximately 70% of patients due to MGMT expression. LP-184 is an acylfulvene-derived prodrug activated by the oxidoreductase PTGR1 that alkylates at N3-adenine, not reported to be repaired by MGMT. This article examines LP-184 efficacy against preclinical GBM models and identifies molecular predictors of LP-184 efficacy in clinical GBM.LP-184 effects on GBM cell viability and DNA damage were determined using cell lines, primary PDX-derived cells and patient-derived neurospheres. GBM cell sensitivities to LP-184 relative to temozolomide and MGMT expression were examined. Pharmacokinetics and CNS bioavailability were evaluated in mice with GBM xenografts. LP-184 effects on GBM xenograft growth and animal survival were determined. Machine learning, bioinformatic tools, and clinical databases identified molecular predictors of GBM cells and tumors to LP-184 responsiveness.LP-184 inhibited viability of multiple GBM cell isolates including temozolomide-resistant and MGMT-expressing cells at IC50 = approximately 22-310 nmol/L. Pharmacokinetics showed favorable AUCbrain/plasma and AUCtumor/plasma ratios of 0.11 (brain Cmax = 839 nmol/L) and 0.2 (tumor Cmax = 2,530 nmol/L), respectively. LP-184 induced regression of GBM xenografts and prolonged survival of mice bearing orthotopic xenografts. Bioinformatic analyses identified PTGR1 elevation in clinical GBM subtypes and associated LP-184 sensitivity with EGFR signaling, low nucleotide excision repair (NER), and low ERCC3 expression. Spironolactone, which induces ERCC3 degradation, decreased LP-184 IC50 3 to 6 fold and enhanced GBM xenograft antitumor responses.These results establish LP-184 as a promising chemotherapeutic for GBM with enhanced efficacy in intrinsic or spironolactone-induced TC-NER-deficient tumors.
Gut microbiota composition and metabolite profiling in smokers: a comparative study between emphysema and asymptomatic individuals with therapeutic implications
Authors: Se Hee Lee, Jiseon Kim, Na Hyun Kim, Ock-Hwa Kim, Chang-Ho Shon, Su Jung Kim, Youngwon Jang, Sunmi Yun, Se Eun Lim, So Yi Jung, Hyun Ju Yoo, Sun-Hee Heo, Sei Won Lee
Journal: Thorax (2023)

Diet has a crucial role in the gut microbiota, and dysbiosis in the gut and lungs has been suggested to be associated with chronic obstructive pulmonary disease. We compared the diet, microbiome and metabolome between asymptomatic smokers and those with emphysema.We enrolled 10 asymptomatic smokers with preserved lung function and 16 smokers with emphysema with severe airflow limitation. Dietary intake information was gathered by a self-reported questionnaire. Sputum and faecal samples were collected for microbial and metabolomics analysis. A murine model of emphysema was used to determine the effect of metabolite supplementation.Despite having a similar smoking history with emphysema patients, asymptomatic smokers had higher values of body mass index, fibre intake and faecal acetate level. Linear discriminant analysis identified 17 microbial taxonomic members that were relatively enriched in the faeces of asymptomatic smokers. Analysis of similarity results showed dissimilarity between the two groups (r=0.287, p=0.003). Higher acetate level was positively associated with forced expiratory volume in one second in the emphysema group (r=0.628, p=0.012). Asymptomatic smokers had a greater number of species associated with acetate and propionate (r>0.6) than did those with emphysema (30 vs 19). In an emphysema mouse model, supplementation of acetate and propionate reduced alveolar destruction and the production of proinflammatory cytokines, and propionate decreased the CD3+CD4+IL-17+ T-cell population in the lung and spleen.Smokers with emphysema showed differences in diet, microbiome and short-chain fatty acids compared with asymptomatic smokers. Acetate and propionate showed therapeutic effects in a smoking-induced murine model of emphysema.
Estimating the attributable fraction of mortality from acute respiratory distress syndrome to inform enrichment in future randomised clinical trials
Authors: Rohit Saha, Tài Pham, Pratik Sinha, Manoj V Maddali, Giacomo Bellani, Eddy Fan, Charlotte Summers, Abdel Douiri, Gordon D Rubenfeld, Carolyn S Calfee, John Gerard Laffey, Daniel Francis McAuley, Manu Shankar-Hari
Journal: Thorax (2023)

Efficiency of randomised clinical trials of acute respiratory distress syndrome (ARDS) depends on the fraction of deaths attributable to ARDS (AF
Tissue-specific features of the T cell repertoire after allogeneic hematopoietic cell transplantation in human and mouse
Authors: Susan DeWolf, Yuval Elhanati, Katherine Nichols, Nicholas R. Waters, Chi L. Nguyen, John B. Slingerland, Natasia Rodriguez, Olga Lyudovyk, Paul A. Giardina, Anastasia I. Kousa, Hana Andrlová, Nick Ceglia, Teng Fei, Rajya Kappagantula, Yanyun Li, Nathan Aleynick, Priscilla Baez, Rajmohan Murali, Akimasa Hayashi, Nicole Lee, Brianna Gipson, Madhumitha Rangesa, Zoe Katsamakis, Anqi Dai, Amanda G. Blouin, Maria Arcila, Ignas Masilionis, Ronan Chaligne, Doris M. Ponce, Heather J. Landau, Ioannis Politikos, Roni Tamari, Alan M. Hanash, Robert R. Jenq, Sergio A. Giralt, Kate A. Markey, Yanming Zhang, Miguel-Angel Perales, Nicholas D. Socci, Benjamin D. Greenbaum, Christine A. Iacobuzio-Donahue, Travis J. Hollmann, Marcel R. M. van den Brink, Jonathan U. Peled
Journal: Science Translational Medicine (2023)

T cells are the central drivers of many inflammatory diseases, but the repertoire of tissue-resident T cells at sites of pathology in human organs remains poorly understood. We examined the site-specificity of T cell receptor (TCR) repertoires across tissues (5 to 18 tissues per patient) in prospectively collected autopsies of patients with and without graft-versus-host disease (GVHD), a potentially lethal tissue-targeting complication of allogeneic hematopoietic cell transplantation, and in mouse models of GVHD. Anatomic similarity between tissues was a key determinant of TCR repertoire composition within patients, independent of disease or transplant status. The T cells recovered from peripheral blood and spleens in patients and mice captured a limited portion of the TCR repertoire detected in tissues. Whereas few T cell clones were shared across patients, motif-based clustering revealed shared repertoire signatures across patients in a tissue-specific fashion. T cells at disease sites had a tissue-resident phenotype and were of donor origin based on single-cell chimerism analysis. These data demonstrate the complex composition of T cell populations that persist in human tissues at the end stage of an inflammatory disorder after lymphocyte-directed therapy. These findings also underscore the importance of studying T cell in tissues rather than blood for tissue-based pathologies and suggest the tissue-specific nature of both the endogenous and posttransplant T cell landscape.
Expression of the excitatory opsin ChRERα can be traced longitudinally in rat and nonhuman primate brains with PET imaging
Authors: Jordi Bonaventura, Matthew A. Boehm, Hank P. Jedema, Oscar Solis, Marco Pignatelli, Xiaowei Song, Hanbing Lu, Christopher T. Richie, Shiliang Zhang, Juan L. Gomez, Sherry Lam, Marisela Morales, Omar A. Gharbawie, Martin G. Pomper, Elliot A. Stein, Charles W. Bradberry, Michael Michaelides
Journal: Science Translational Medicine (2023)

Optogenetics is a widely used technology with potential for translational research. A critical component of such applications is the ability to track the location of the transduced opsin in vivo. To address this problem, we engineered an excitatory opsin, ChRERα (hChR2(134R)-V5-ERα-LBD), that could be visualized using positron emission tomography (PET) imaging in a noninvasive, longitudinal, and quantitative manner. ChRERα consists of the prototypical excitatory opsin channelrhodopsin-2 (ChR2) and the ligand-binding domain (LBD) of the human estrogen receptor α (ERα). ChRERα showed conserved ChR2 functionality and high affinity for [18F]16α-fluoroestradiol (FES), an FDA-approved PET radiopharmaceutical. Experiments in rats demonstrated that adeno-associated virus (AAV)-mediated expression of ChRERα enables neural circuit manipulation in vivo and that ChRERα expression could be monitored using FES-PET imaging. In vivo experiments in nonhuman primates (NHPs) confirmed that ChRERα expression could be monitored at the site of AAV injection in the primary motor cortex and in long-range neuronal terminals for up to 80 weeks. The anatomical connectivity map of the primary motor cortex identified by FES-PET imaging of ChRERα expression overlapped with a functional connectivity map identified using resting state fMRI in a separate cohort of NHPs. Overall, our results demonstrate that ChRERα expression can be mapped longitudinally in the mammalian brain using FES-PET imaging and can be used for neural circuit modulation in vivo.
Alterations in the gut microbiome implicate key taxa and metabolic pathways across inflammatory arthritis phenotypes
Authors: Kelsey N. Thompson, Kevin S. Bonham, Nicholas E. Ilott, Graham J. Britton, Paula Colmenero, Samuel J. Bullers, Lauren J. McIver, Siyuan Ma, Long H. Nguyen, Andrew Filer, India Brough, Claire Pearson, Caroline Moussa, Vinod Kumar, Lilian H. Lam, Matthew A. Jackson, April Pawluk, Serafim Kiriakidis, Peter C. Taylor, Lucy R. Wedderburn, Brian Marsden, Stephen P. Young, Dan R. Littman, Jeremiah J. Faith, Arthur G. Pratt, Paul Bowness, Karim Raza, Fiona Powrie, Curtis Huttenhower, Coziana Ciurtin, Claudia Mauri
Journal: Science Translational Medicine (2023)

Musculoskeletal diseases affect up to 20% of adults worldwide. The gut microbiome has been implicated in inflammatory conditions, but large-scale metagenomic evaluations have not yet traced the routes by which immunity in the gut affects inflammatory arthritis. To characterize the community structure and associated functional processes driving gut microbial involvement in arthritis, the Inflammatory Arthritis Microbiome Consortium investigated 440 stool shotgun metagenomes comprising 221 adults diagnosed with rheumatoid arthritis, ankylosing spondylitis, or psoriatic arthritis and 219 healthy controls and individuals with joint pain without an underlying inflammatory cause. Diagnosis explained about 2% of gut taxonomic variability, which is comparable in magnitude to inflammatory bowel disease. We identified several candidate microbes with differential carriage patterns in patients with elevated blood markers for inflammation. Our results confirm and extend previous findings of increased carriage of typically oral and inflammatory taxa and decreased abundance and prevalence of typical gut clades, indicating that distal inflammatory conditions, as well as local conditions, correspond to alterations to the gut microbial composition. We identified several differentially encoded pathways in the gut microbiome of patients with inflammatory arthritis, including changes in vitamin B salvage and biosynthesis and enrichment of iron sequestration. Although several of these changes characteristic of inflammation could have causal roles, we hypothesize that they are mainly positive feedback responses to changes in host physiology and immune homeostasis. By connecting taxonomic alternations to functional alterations, this work expands our understanding of the shifts in the gut ecosystem that occur in response to systemic inflammation during arthritis.
Pharmaco-proteogenomic characterization of liver cancer organoids for precision oncology
Authors: Shuyi Ji, Li Feng, Zile Fu, Gaohua Wu, Yingcheng Wu, Youpei Lin, Dayun Lu, Yuanli Song, Peng Cui, Zijian Yang, Chen Sang, Guohe Song, Shangli Cai, Yuanchuang Li, Hanqing Lin, Shu Zhang, Xiaoying Wang, Shuangjian Qiu, Xiaoming Zhang, Guoqiang Hua, Junqiang Li, Jian Zhou, Zhi Dai, Xiangdong Wang, Li Ding, Pei Wang, Daming Gao, Bing Zhang, Henry Rodriguez, Jia Fan, Hans Clevers, Hu Zhou, Yidi Sun, Qiang Gao
Journal: Science Translational Medicine (2023)

Organoid models have the potential to recapitulate the biological and pharmacotypic features of parental tumors. Nevertheless, integrative pharmaco-proteogenomics analysis for drug response features and biomarker investigation for precision therapy of patients with liver cancer are still lacking. We established a patient-derived liver cancer organoid biobank (LICOB) that comprehensively represents the histological and molecular characteristics of various liver cancer types as determined by multiomics profiling, including genomic, epigenomic, transcriptomic, and proteomic analysis. Proteogenomic profiling of LICOB identified proliferative and metabolic organoid subtypes linked to patient prognosis. High-throughput drug screening revealed distinct response patterns of each subtype that were associated with specific multiomics signatures. Through integrative analyses of LICOB pharmaco-proteogenomics data, we identified the molecular features associated with drug responses and predicted potential drug combinations for personalized patient treatment. The synergistic inhibition effect of mTOR inhibitor temsirolimus and the multitargeted tyrosine kinase inhibitor lenvatinib was validated in organoids and patient-derived xenografts models. We also provide a user-friendly web portal to help serve the biomedical research community. Our study is a rich resource for investigation of liver cancer biology and pharmacological dependencies and may help enable functional precision medicine.
Signatures of AAV-2 immunity are enriched in children with severe acute hepatitis of unknown etiology
Authors: Moriah M. Mitchell, Yumei Leng, Suresh Boppana, William J. Britt, Luz Helena Gutierrez Sanchez, Stephen J. Elledge
Journal: Science Translational Medicine (2023)

Severe acute hepatitis of unknown etiology in children is under investigation in 35 countries. Although several potential etiologic agents have been investigated, a clear cause for the liver damage observed in these cases remains to be identified. Using VirScan, a high-throughput antibody profiling technology, we probed the antibody repertoires of nine cases of severe acute hepatitis of unknown etiology treated at Children's of Alabama and compared their antibody responses with 38 pediatric and 470 adult controls. We report increased adeno-associated dependoparvovirus A (AAV-A) breadth in cases relative to controls and adeno-associated virus 2 (AAV-2) peptide responses that were conserved in seven of nine cases but rarely observed in pediatric and adult controls. These findings suggest that AAV-2 is a likely etiologic agent of severe acute hepatitis of unknown etiology.